Does Arterial Spin-labeling MR Imaging–measured Tumor Perfusion Correlate with Renal Cell Cancer Response to Antiangiogenic Therapy in a Mouse Model?1

• Published in: Radiology Vol. 251; no. 3; p. 731
• Main Authors: Rachel Schor-Bardach, David C. Alsop, Ivan Pedrosa, Stephanie A. Solazzo, Xiaoen Wang, Robert P. Marquis, Michael B. Atkins, Meredith Regan, Sabina Signoretti, Robert E. Lenkinski, S. Nahum Goldberg
• Format: Journal Article
• Language: English
• Published: Radiological Society of North America 01-06-2009
• ISSN: 0033-8419; 1527-1315
• DOI: 10.1148/radiol.2521081059

Purpose: To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic
therapy can predict later resistance to therapy.
Materials and Methods: Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma
(RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once
tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498
(3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed
and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences.
Results: Baseline blood flow was 80.1 mL/100 g/min ± 23.3 (standard deviation) for A498, 75.1 mL/100 g/min ± 28.6 for 786-0, and 10.2
mL/100 g/min ± 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min ± 7.6) in flow, whereas flow
decreased in all treated A498 on day 14 (47.9 mL/100 g/min ± 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min ± 8.7) ( P = .003 and .03, respectively). For A498, lowest values were measured at 28–42 days of receiving sorafenib. Regions of increased
flow occurred on days 35–49, 17–32 days before documented tumor growth and before significant increases in mean flow (day
77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable
tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent
days ( P > .99).
Conclusion: ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib.
© RSNA, 2009